The control of diseases caused by blood residing parasites is of major importance in veterinary medicine. Parasitic infestations of the blood and blood-forming organs in both domestic animals and in wild animals results in substantial direct economic loss each year owing to death and debilitation. Further economic losses are incurred by the need to separate diseased animals and the necessary and attendant restrictions on herd movements imposed by quarantine laws. The most significant losses from blood residing parasites are caused by parasitic worms, particularly filaria and by parasitic protozoa especially plasmodiam and babesia.
Among the filaria diseases, canine heart worm caused by Dirofilaria immitis is prevalent along the East and Gulf coasts of the United States where as many as 50% of dogs may be affected. Filariasis or heart worm disease appears to be a growing problem throughout the United States and other countries and is not confined to dogs, but may be found in other animal species such as cats, seal, brown bear, wolverine, coyotes and rarely in humans. Presently available treatments and therapeutic agents are limited and are not entirely effective. The drugs currently in use include Levamisole (Tetramisole hydrochloride) and Arsenamide (Thiacetarsamide Sodium).
Animal diseases caused by blood residing parasitic protozoa are comon among horses, cattle, goats and sheep and include equine babesiasis, bovine babesiasis, anaplasmosis and piroplasmosis. These diseases are characterized by the presence of parasitic protozoa in the blood stream of the infected animal where the protozoa attack the red blood cells, causing anemia.
Piroplasmosis in horses, known as Equine Piroplasmosis, equine babesiasis, or equine malaria, is an acute, subacute and/or chronic hemoprotozoan infectious disease of solipeds, caused by Babesis caballi, or B. equi, and characterized in clinical cases by intermittent fever, weakness, constipation, anemia, icterus, and edema. This disease is reported to be world-wide. The infecting protozoa may be transmitted by various species of ticks, by parenteral injection of blood or organ emulsion, or by intrauterine transmission. Horses, mules, donkeys, and zebra are especially susceptible to this disease. Peracute cases are fatal, while less severe acute and subacute cases may recover. Currently available treatments are not generally effective, and owing to difficulty in detecting the disease, treatment is frequently started too late. Commonly used therapeutic agents are birenil, acaprin, and acriflavin. However, these are reported only to reduce the number of parasites.
Piroplasmosis and babesiasis in cattle, also known as Texas fever, is an infectious disease of bovines caused by Babesia digeminum which affects erythrocytes and is primarily propagated by ticks. It is characterized by an acute condition with or without hemoglobinuria and a chronic state of latent infection. Animals infected with Texas fever in a very acute condition have little chance of surviving without treatment. Common therapeutic agents include trypan blue, acaprin, phenadrine, and berenil.
Anaplasmosis of cattle, sheep and goats is caused by infection with Anaplasma spp. The causative agent in sheep and goats is A. ovis. The infectious disease of cattle is caused by progressive anemia due to erythrocyte destruction. The disease is widely distributed in the warmer climates of the United States and transmitted by blood-sucking insects as well as by mechanical means. Bovine is the parasitic natural host, while buffalo, zebra, deer and other wild ruminants act as natural reservoirs. The prognosis for this disease is 50 to 70% recovery, and recovered animals continue to be a hazard due to their carrier condition. Treatment for this disease may be effected by utilizing antibiotics, such as terramycin, aureomycin or tetracyclines, if given in the early stages of infection. Carrier eradication may be effected with aurofac in cattle feed for a prolonged period of time. Anaplasmosis is now present in 40 of the 50 states of the United States and is reported to cost this country $35,000,000 annually.
Parasitic protozoal infestations are difficult diseases to eradicate due to the fact that there are a large number of insects capable of being carriers of these diseases. Furthermore, the armament of drugs utilized to halt the proliferation of these parasites may lose their efficacy due to the evolution of drug resistant protozoic strains.
Anti-malarial related research indicates that there are basically two known mechanisms responsible for chemotherapeutic anti-malarial action as well as related protozoal diseases. The first mechanism responsible for the action of the oldest known antimalarial agent, quinine, is that of non-specific DNA binding or intercalation. The second proposed mechanism is specific to protozoic diseases. Protozoa incorporate para-aminobenzoic acid into folic acid, a process which does not occur in mammals in their metabolic machinery and require a supply of para-amino benzoic acid in order to synthesize their own folinic acid. Folic acid enzyme antagonists therefore have been found to exhibit anti-protozoal activity. Interference with the enzymatic machinery of this synthetic pathway may be responsible for this selective anti-protozoal action. Drugs known to act in this fashion include chloroguanide, cycloguanial pamoate, pyrimethamine and its derivatives, as well as sulphamides and sulphones.
Among the folinic acid antagonists, the biguanide members may be, in some cases, transformed in the host body to form active triazine metabolites. However, the triazine metabolite of chloroquanide has little or no usefulness in the therapy of humans and monkeys due to its rapid excretion from the body. Moreover, this latter class of compounds, that is, the folinic acid inhibitors, are most susceptible to a loss of efficacy due to the appearance of therapeutically resistant strains of protozoa. In fact, P. berghei is known as a pyrimethamine resistant protozoal strain. Structural changes in the triazine rings of the presumably active form of these anti-protozoal drugs, as well as its method of administration, may modify the activity unpredictably as well as alter the rate of excretion of the drug from the host body. For example, while in malaria cases, chloroguanide is rapidly excreted from the body when in its triazine form and has little or no usefulness, chloroguanide triazine pamoate, when tested with P. berghei infected mice, has good and lasting effects with a single muscular injection and is not excreted rapidly from the host body. Owing to such unpredictability and the limited drugs available for treatment of animal diseases caused by blood-residing parasites, there is need for effective drugs for use in the treatment of these animal diseases.